Proximity-ligation metagenomics reveals disease-specific mobilome dynamics in disrupted gut ecosystems

Distinct ecological pressures shape accumulation of antimicrobial resistance and virulence genes in the gut microbiome. Using proximity ligation shotgun metagenomics to resolve host–mobilome relationships, we analyzed microbiomes from two patient cohorts: recurrent Clostridioides difficile infection (rCDI) and cirrhosis. While rCDI reflects antibiotic-driven disruption, cirrhosis-driven microbiome changes result from altered gut physiology. We found increased chromosomal determinants of antibiotic resistance in both, but plasmid-mediated amplification was more evident in rCDI.